Activated protein C resistance impact on Syrian candidates for in vitro fertilisation and the benefit of anticoagulation therapy: a retrospective cohort study

Abstract

Activated protein C resistance (APCR) is a common thrombophilia, caused mainly by a mutation. The impact of APCR on the efficacy of In Vitro Fertilization (IVF) are still unclear, and no solid recommendations for its management were published. To investigate the effect of APCR on IVF outcomes and assess the efficacy of our management protocol, we retrospectively scanned the medical records of women who were tested with APCR assay in 2019 at our fertility centre. The 66 women (12%) positive for APCR had lower odds of reaching clinical pregnancies after IVF 0.18 [95% CI: 0.07–0.47] and fewer live births. The administration of low-molecular-weight heparin and aspirin associated with more implantation in treated compared to untreated APCR-positive women with an odds ratio of 43.2 [7.51–248.6]. In conclusion, APCR negatively affects the number of clinical pregnancies after IVF, but anticoagulation therapy can mitigate this effect and significantly increase clinical pregnancies.

Impact Statement

• What is already known on this subject? The evidence about the impact of APCR on IVF outcomes is still inconclusive. According to the Canadian guideline, routine screening for thrombophilia in patients with recurrent pregnancy loss is not recommended. No clear recommendations regarding the management of APCR in the planning for IVF are yet available.

• What do the results of this study add? APCR significantly increases implantation failure among infertile women who conduct IVF. Management of APCR using LMWH and aspirin was effective in mitigating this effect and increasing successful implantation.

• What are the implications of these findings for clinical practice and/or further research? Our findings can support the recommendation to include APCR assay in the routine tests for infertile women conducting IVF, and suggest the combination between LMWH and aspirin as an effective therapy to increase successful implantation in APCR positive candidates. However, more controlled clinical trials are still needed to confirm our results.

Keywords:

• Activated protein C resistance
• factor V Leiden
• in vitro fertilisation
• implantation failure
• thrombophilia

Acknowledgments

The authors thank Racha Mirza, MD; and Fatima Zarzour, MD for their help in data collection; Marah Alsalkini, MD; Hany Habib, MD for their help in revising the manuscript.

Disclosure statement

No conflict of interest was reported by the authors.

Author contributions

RS designed the study, helped in data collection, and analysed the data. RS and MGA drafted the manuscript. MGA designed the data collection tool. IH revised the data collection tool, the data analysis, and critically edited the manuscript. ID collected most of the data. MA supervised the project, and reviewed the manuscript. All authors have read and approved the final manuscript.

Data availability statement

All the data are available from the corresponding author on reasonable request.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or non-for-profit sectors.